1. Field of the Invention
This invention relates to valves for delivering metered doses of aerosol formulations, and to such valves having a positive fill metering chamber. In another aspect this invention relates to methods of filling an aerosol canister. In yet another aspect this invention relates to methods of delivering a metered dose of an aerosol formulation.
2. Description of the Related Art
Conventional chlorofluorocarbon based medicinal aerosol formulations generally contain a relatively nonvolatile component (e.g., trichlorofluoromethane, propellant 11), a surfactant, a drug, and a volatile propellant system (e.g., a combination of dichlorodifluoromethane, propellant 12, and dichlorotetrafluoroethane, propellant 114). Likewise certain formulations based on alternative non-CFC propellants such as 1,1,1,2-tetrafluoroethane or 1,1,1,2,3,3,3-heptafluoroethane can contain nonvolatile components such as surfactants and cosolvents (e.g., an alcohol such as ethanol). Such formulations can be filled into individual aerosol canisters by one of two conventional methods: pressure filling or cold filling. Cold filling generally involves the preparation of a mixture of the nonvolatile components at room temperature and ambient pressure to form a concentrate. This concentrate is then cooled to a temperature at which the remaining components are liquid at ambient pressure. The volatile components are also cooled and added to the concentrate to afford a liquid formulation that is filled into individual canisters, also at reduced temperature. A valve is crimped into place on the canister and the finished product is allowed to warm to ambient temperature.
Pressure filling is generally a two step process that involves the same preparation of a concentrate containing nonvolatile components. An appropriate amount of the concentrate is metered into an individual canister at ambient temperature and pressure. A valve is then crimped into place. The volatile components are then added to the canister via the valve under pressure sufficient to liquify the volatile components.
There are several deficiencies in conventional pressure filling methods. For one, conventional pressure fill valves generally involve a gasket or similar seal past which the propellant is forced under pressure great enough to displace or deform the gasket or seal. The gasket or seal functions as a one-way valve. Once a device involving such a gasket or seal is filled, the pressure of the propellant on the gasket or seal is sufficient to prevent release of the propellant. However, the fact that the gasket or seal must be displaced or deformed results in the formulation being passed through a small passageway, producing relatively high backpressures which in turn will limit the speed at which filling can be carried out. Further, since backpressures are relatively high it is problematic to fill relatively viscous formulations. Hence the need to fill certain formulations in the two stage manner described above in order to avoid forcing viscous materials through a small passageway. A resultant disadvantage in conventional pressure filling lies in the fact that it involves two processing steps.
Certain metered dose valves for use in connection with pharmaceutical aerosol formulations have deficiencies relating to the fact that the metering tank must be refilled with formulation before the valve stem is depressed to discharge a dose. In some instances the metering tank holds a dose of formulation for an extended period of time before the dose is discharged. These deficiencies have been addressed in U.S. Pat. No. 4,819,834 (Thiel) by a valve design in which a metering chamber is simultaneously created and filled upon depressing of the valve stem. Such valves are referred to as "positive fill valves". Such valves, however, still require that a seal or gasket be displaced upon filing.
It can be seen that a valve that overcomes the several disadvantages mentioned above in connection with pressure filling while maintaining the known advantages of a positive fill metering chamber would be of significant utility.